Angioplasty and stenting for peripheral artery disease (PAD) of the femoropopliteal artery segment, consisting of the superficial femoral artery (SFA) and popliteal artery (PA), carries the highest rate of reconstruction failure primarily because it undergoes large deformations during flexion of the limb. Our preliminary data demonstrate that previously published limb-induced deformations of the SFA and PA are markedly underestimated, and that certain stent designs are not able to accommodate these severe deformations. We propose to precisely quantify the mechanical environments of the SFA and PA in order to determine the optimal patient and lesion- specific stent for the SFA and PA. This will be accomplished through 3 Specific Aims. In Aim 1 we will determine the 3D bending, torsion and compression of the SFA and PA as a result of limb flexion in human cadavers using our new intra-arterial marker technique, CTA, and image analysis. In Aim 2 we will determine the biaxial mechanical properties of SFA and PA from human tissue donors with PAD, along with the mechanical properties of 5 commonly used self-expanding nitinol PAD stents. In Aim 3 we will use the data on femoropopliteal artery flexions (Aim 1) and SFA, PA and PAD stent mechanical properties (Aim 2), to build a computational model of the stented SFA and PA. This model will then be subjected to limb flexion induced deformations to determine the mechanical stress resulting from the interaction of the stent with the artery. A comparison of each of the 5 stents under identical conditions, including a systematic study of the effects of age, diabetes and lesion calcification on these mechanical stresses, will allow identification of the optimal stet for the SFA and PA in patients with different clinical and lesion characteristics. The capability o our model to predict areas where restenosis will occur in the stented SFA/PA will for the first time be clinically validated in PAD patients by comparing the areas of high stress in the patient-specific models to the areas of restenosis visualized by CTA 6 months after stenting. The ability to rationally select patient and lesion-specific stents for the SFA and PA will produce more durable reconstructions and have an immediate direct translational impact benefiting PAD patients with claudication and critical limb ischemia. Our precise description of the human SFA and PA mechanical environments will greatly advance our knowledge of PAD pathophysiology and will allow the development of a better stent for the SFA and PA. By creating vital, currently unavailable computational model input data and taking the initial steps towards clinical validation, our study will serve as a foundation for larger-scale, more cost-effective in silico comparative effectiveness studies of current and future PAD stents and help advance the new paradigm of patient-specific modeling and medicine.